Viruses are obligate parasites causing a wide variety of diseases in humans, ranging from the common cold to cancer. There is no antiviral agent available for widespread therapeutic application. Typically the defense against virus disease is the immune system of the host. The most promising solution to viral diseases in humans and other higher animals is the development of vaccines based on synthetic polypeptides from regions of the antigen that evoke strong response from the immune system. To develop a rational strategy for such vaccines the relationship between the antibody and antigen must be known in detail. How is a virus neutralized by an antibody? Will an antibody produced by any region of the antigen lead to neutralization? It is possible for regions of the antigen that do not normally evoke antibody response to bind an antibody if it is elicited by the same antigen amino acid sequence in a synthetic polypeptide? What is the role of primary and tertiary structure in binding of the antibody to the antigen. The objectives of this proposal are designed to answer these questions. The structure of cowpea mosaic virus (CpMV) will first be solved at 2.8 Angstroms resolution using single crystal X-ray diffraction. The virus crystallizes in space group I23 a = 3.17 Angstroms. The structure will be refined using the Hendrickson Konnert procedure. Currently the structure has been solved at 5.5 Angstroms resolution using a single isomorphous derivative and real space electron density and phase refinement. When the structure has been fully interpreted a reproducible crystal form of CpmV (P6122 a = 450; c = 1038 Angstroms) containing 300 Angstrom channels parallel to the crystal axes will be used to study the binding of monoclonal antibodies to the virus particle. Approximately thirty to forty antigenic sites should be exposed in the hexagonel crystals. Conditions must be found in which antibodies bind without disturbing the crystal lattice. The antibody-virus complex will be solved using the virus structure determined at 2.8 Angstroms in the cubic cell as the phasing model. Data to 3.5 Angstroms have previously been collected from the native virus in the hexagonal cell. CpMV displays protein sequence homology with the animal picorna viruses in the nonstructural proteins (polymerase, VpG, and protease). Extensive comparisons will be made between the CpMV structure and the polio and rhinovirus structures.